The basic abnormality in cystic fibrosis, which is the most common fatal heredity disease in the U.S., occurs inthe exocrine glands, although the nature of the defect is unknown. Of the several hypotheses which have been advanced, an abnormality in the adrenergic regulatory system appears to be the most promising. However, the clinical data necessary to test this hypothesis are not available. We propose to determine if patients with cystic fibrosis have alterations in their adrenergic regulatory systems. These regulatory systems can be considered conceptually to consist of a number of components, including first messenger, receptor, second messenger and biochemical or functional effect. We propose to study these four components in two interrelated adrenergic regulatory systems, namely the beta adrenergic system in polymorphonuclear (PMN) leukocytes and the alpha-2 adrenergic system in platelets. The specific parameters to be studied: the concentrations of catecholamine, glycogen and cyclic nucleotides; the beta and alpha-2 adrenergic receptor binding sites; the enzymes adenylate cyclase, phosphodiesterase, glycogen synthase and phosphorylase; and platelet aggregation. The proposed studies will provide important new information which will increase our understanding of the etiology of the cystic fibrosis and hopyfully suggest new, rational approaches to the treatment of patients with CF.